Prolonged vs intermittent infusion of piperacillin/tazobactam in critically ill patients: a narrative and systematic review

J Crit Care. 2014 Dec;29(6):1089-95. doi: 10.1016/j.jcrc.2014.07.033. Epub 2014 Aug 7.

Abstract

Purpose: The purpose of this study is to review the rationale of prolonged (ie, extended or continuous) infusion of piperacillin/tazobactam (PIP/TAZ) in critically ill patients and to perform a systematic review that compare the effectiveness of prolonged infusion with intermittent bolus of PIP/TAZ.

Materials and methods: A search of Medline, Web of Science, Embase, and Cochrane databases was conducted up to April 2014. For systematic review, studies comparing the effectiveness of prolonged and bolus administration of PIP/TAZ were included. The level of evidence is determined using best-evidence synthesis, which consisted of 5 possible levels of evidence: strong, moderate, limited, conflicting, or no evidence.

Results: The pharmacokinetic/pharmacodynamic studies that account for an eventual benefit of prolonged PIP/TAZ infusion were reviewed. In the systematic review, 1 randomized controlled trial was identified that showed higher "cure" in the prolonged than in the intermittent infusion group, yet the chosen clinical outcome in this study, decline in mean Acute Physiology and Chronic Health Evaluation II score is controversial. Of 6 retrospective cohort studies, 4 showed either less mortality, a higher clinical cure rate, or shorter length of hospital stay with prolonged PIP/TAZ treatment. The level of evidence supporting a better clinical outcome with prolonged infusion of PIP/TAZ is moderate.

Conclusion: Pharmacokinetic/pharmacodynamic studies provide a robust rationale to prefer prolonged above intermittent infusion of PIP/TAZ. However, although some studies suggest a better outcome in critically ill patients receiving prolonged infusion, the level of evidence is moderate.

Keywords: Infection; Intensive care; Pharmacodynamic; Pharmacokinetic; Piperacillin/tazobactam; Prolonged infusion.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Aged
  • Aged, 80 and over
  • Anti-Bacterial Agents / administration & dosage*
  • Anti-Bacterial Agents / adverse effects
  • Anti-Bacterial Agents / blood
  • Anti-Bacterial Agents / pharmacokinetics
  • Critical Illness / therapy*
  • Female
  • Humans
  • Infusions, Intravenous
  • Length of Stay
  • Male
  • Middle Aged
  • Penicillanic Acid / administration & dosage
  • Penicillanic Acid / adverse effects
  • Penicillanic Acid / analogs & derivatives*
  • Penicillanic Acid / blood
  • Penicillanic Acid / pharmacokinetics
  • Piperacillin / administration & dosage
  • Piperacillin / adverse effects
  • Piperacillin / blood
  • Piperacillin / pharmacokinetics
  • Piperacillin, Tazobactam Drug Combination
  • Randomized Controlled Trials as Topic
  • Retrospective Studies
  • beta-Lactamase Inhibitors / administration & dosage*
  • beta-Lactamase Inhibitors / adverse effects
  • beta-Lactamase Inhibitors / blood
  • beta-Lactamase Inhibitors / pharmacokinetics

Substances

  • Anti-Bacterial Agents
  • beta-Lactamase Inhibitors
  • Piperacillin, Tazobactam Drug Combination
  • Penicillanic Acid
  • Piperacillin